Reasearch On Targeting Nanoprobes Designed For VX2 Tumors Identification In CT/MR Bimodal Imaging

Part One The uitility of nano-probe in tumor imaging andbiodistribution in VX2 tumor model by CT / MR imagingObjective: Imaging technology is essential to early diagnosis of tumor.Nano-materials with surface active centers,large surface area,strong adsorption capacity,high surface reactivity,low toxicity,Which can be used as a contrast agent for imaging,In this study,we designed a new nanoparticles as bimodal CT / MR contrast agent for tumor imaging.Methods: Ba Gd F5 nanoparticles were synthesized by hydrothermal method and surface modified by PEG.Characteristic of material such as particle size,hydration kinetic diameter,transform infrared spectrum analysis were tested.Standard MTT method evaluated nanoparticles cytotoxicity,Biological toxicity were tested in Kung Ming mouse.In vitro conditions,We compared the nanoparticles with CT contrast agents iohexol and MR imaging contrast agents gadopentetate dimeglumine.In vivo situation,nude mice bearing VX2 tumor were used as animal model,tumor metabolism was evaluated by FDG PET / CT.Nanoprobes pharmacokinetics was explored by CT imaging.The enhancement of the mass were measured by CT value in CT imaging and T1 value of T1 Mapping sequence in MR imaging.Results: TEM images showed that the diameter of nanoparticle was about 10 nm,with pebble-shape,uniform size.After PEG modified,Ba Gd F5-PEG had good biocompatibility and water solubility,no significant cytotoxicity and toxicity,hydration kinetics diameter of nanoparticle was 51.7nm,Zeta potential was 48.5mv.In vitro conditions: X-ray attenuation coefficient of Ba Gd F5 was greater than iohexol,Gd relaxivity r1 of Ba Gd F5 was 1.58.In vivo conditions: PET / CT imaging: The No.3 mouse was excluded because of low tumor glucose metabolism of VX2 tumor.CT imaging: after injection of nano-materials,The enhancement of liver and spleen were remarkable,which lasted until 12 h after injection of nano-materials,The CT value of tumor ranged from 53 HU to 65 HU,increased by 23%.MR imaging: T1 values of the tumor ranged from 1600 ms to 1100 ms at 0.5h after injection of nanomaterials,decreased by 31%.Conclusion: We designed a CT / MR multimodal biocompatible nanomaterial Ba Gd F5-PEG,mainly metabolized by the liver and spleen and enhancement of tumor were also observed.Part Two The reasearch about targeted effect of nanoprobes to VX2 tumor in CT imaging and differentatial diagnosis between VX2tumor and inflammation in MR imagingObjective: Ba Gd F5-PEG-RGD nanoprobe modified by RGD peptide was targeted to ?v?3 integrin protein which highly expressed in VX2 tumor cells,thus it can be the targeted contrast agent in CT imaging.Besides,we explored the change of targeted nanomaterial Ba Gd F5-PEG-RGD in tumor and inflammation lesion.Methods: Ba Gd F5 nanoparticles was synthesized by hydrothermal method and modified by PEG,After connecting RGD,Ba Gd F5-PEG-RGD targeted nanoparticle was prepared.Including hydration kinetic diameter,transform infrared spectrum analysis,transverse relaxation performance in MRI imaging,the characteristic of the nanomaterial were tested.There were two types animal model in our study,VX2 tumor model in nude mice and tumor-inflammation model in New zealand rabbits.Tumor metabolism was evaluated by FDG PET / CT.In CT imaging,nanoprobes pharmacokinetics and the enhancemant of tumor lesion were explored in nude mice VX2 tumor model.In MR imaging,dynamic contrast-enhanced MR LAVA flex sequence was used for dynamic monitoring T1 signal value changes in rabbit tumor and inflammation lesion.Results: The hydration kinetic diameter of Ba Gd F5-PEG-RGD was 55.05 nm,Zeta potential was 49.1mv.connected with RGD,relaxation rate 1 / T1 of nanoparticles ranged from 1.58 to 1.67.The CT value of tumor increased from 54 HU to 85 HU in CT imaging at 12 h after injection of nanomaterials,increased by 57%.T1 signal value increased markedly in tumor lesion than it in inflammation lesion.The T1 signal value of tumor had not decrease untill 1.5h after the injection meanwhile the T1 signal value of the inflammation continued rising.The T1 signal value of muscles had no significant change.Conclusion: After connecting RGD cyclic peptide,Ba Gd F5-PEG-RGD realized VX2 tumor targeting imaging.The metabolism of Ba Gd F5-PEG-RGD in tumors and inflammatory lesions was different,which need a further study.